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Gut microbiota-dependent phenylacetylglutamine in cardiovascular disease:current knowledge and new insights

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Frontiers of Medicine 2024年第1期18卷 31-45页

作者： Yaonan Song Haoran Wei Zhitong Zhou Huiqing Wang Weijian Hang Junfang Wu Dao Wen Wang division of Cardiology Department of Internal MedicineTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological disorders Wuhan430030China

Phenylacetylglutamine(PAGln)is an amino acid derivate that comes from the amino acid *** are increasing studies showing that the level of PAGln is associated with the risk of different cardiovascular *** this review,we discussed the metabolic pathway of PAGln production and the quantitative measurement methods of *** summarized the epidemiological evidence to show the role of PAGln in diagnostic and prognostic value in several cardiovascular diseases,such as heart failure,coronary heart disease/atherosclerosis,and cardiac *** underlying mechanism of PAGln is now considered to be related to the thrombotic potential of platelets via adrenergic ***,other possible mechanisms such as inflammatory response and oxidative stress could also be induced by ***,since PAGln is produced across different organs including the intestine,liver,and kidney,the cross-talk among multiple organs focused on the function of this uremic toxic ***,the prognostic value of PAGln compared to the classical biomarker was discussed and we also highlighted important gaps in knowledge and areas requiring future investigation of PAGln in cardiovascular diseases.

关键词： PAGln cardiovascular disease gut microbiota uremic metabolite biomarker

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin Department of Affective disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada Department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory ***,anti-inflammatory treatment has shown partial effectiveness in alleviating depression *** barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory *** our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold *** is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory *** the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo *** the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo *** analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive *** findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy

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Science China(Life Sciences) 2024年第6期67卷 1155-1169页

作者： Shuai Yuan Xudong Zhang Jiabing Zhan Rong Xie Jiahui Fan Beibei Dai Yanru Zhao Zhongwei Yin Qian Liu Dao Wen Wang Huaping Li Chen Chen division of Cardiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological disorders Wuhan 430030China Department of Forensic Medicine Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

CFIRL is a long noncoding RNA(lnc RNA),we previously identified as the most significantly upregulated lnc RNA in the failing hearts of patients with dilated cardiomyopathy(DCM).In this study,we determined the function of CFIRL and its role in ***-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing *** knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction(TAC)-induced cardiac dysfunction and fibrosis in *** of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to *** knockdown attenuated these ***,RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1,a newly identified noncanonical transcriptional factor,to activate ***-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy,which can be prevented by CFIRL *** findings uncover the critical role of CFIRL,a fibroblast-associated lnc RNA,in heart failure by facilitating crosstalk between fibroblasts and *** knockdown might be a potent strategy to prevent cardiac remodeling in heart failure,particularly in DCM.

关键词： lncRNA fibroblast fibrosis dilated cardiomyopathy heart failure

The immune system:uncharted pathways between senses and the brain

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Neural Regeneration Research 2024年第6期19卷 1173-1174页

作者： Noelia Casares Mar Cuadrado-Tejedor Ana García-Osta Juan JoséLasarte Immunology and Immunotherapy Program Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain division of Gene Therapy for Neurological disorders Centre for Applied Medical Research(CIMA)University of NavarraIDISNAPamplonaSpain Pathology Anatomy and Physiology DepartmentSchool of MedicineUniversity of NavarraIDISNAPamplonaSpain

Humans and animals use the classic five senses-sight,hearing,touch,smell,and taste-to detect and monitor their environment,with the sense of position and movement often referred to as the sixth *** perception of external signals through the senses is essential to an organism's survival,transmitting signals to the central nervous system(CNS)and prompting physiological changes in other biological *** addition to the direct effects of sense-induced mediators in the brain.

关键词： prompt system transmitting

Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents

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General Psychiatry 2024年第2期37卷 216-223页

作者： Shuyin Xu Yumeng Ju Xiyu Wei Wenwen Ou Mohan Ma Guanyi Lv Xiaotian Zhao Yaqi Qin Yunjing Li Liang Li Mei Huang Siqi Yang Yimei Lu Yafei Chen Junwu Liu Jin Liu Bangshan Liu Yan Zhang Department of Psychiatry National Clinical Research Center for Mental Disordersand National Center for Mental DisordersThe Second Xiangya Hospital of Central South UniversityChangshaHunanChina Mental Health Institute of Central South University China National Technology Institute on Mental DisordersHunan Technology Institute of PsychiatryHunan Key Laboratory of Psychiatry and Mental HealthHunan Medical Center for Mental HealthChangshaHunanChina

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide *** The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and *** 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire(PHQ-9)and the Generalized anxiety Disorder Scale,and 716 adolescents who scored≥5 on both scales were selected as *** analysis was used to identify the network structure of depressive symptoms and anxiety *** were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9.A comparison was made between the depression-anxiety symptom networks of the two ***‘Restlessness’,‘sad mood’and‘trouble relaxing’were the most prominent central symptoms in the depression-anxiety symptom network,and‘restlessness’,‘nervousness’and‘reduced movement’were the bridge symptoms in this network.‘Sad mood’was found to be directly related to‘suicide ideation’with the highest *** network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group,with‘restlessness’and‘sad mood’exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation *** Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

关键词： symptoms adolescent assessed

Cell-type specific examination of central amygdala dopamine receptor 2 expressing neurons as a translational target for pharmacological enhancement of extinction

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中国药理学与毒理学杂志 2017年第10期31卷 952-953页

作者： Kenneth M.MCCULLOUGH Georgette GAFFORD Filomene G MORRISON Kerry J RESSLER division of depression & anxiety disorders Mc Lean HospitalDepartment of PsychiatryHarvard Medical School Behavioral Neuroscience Department of Psychiatry and Behavioral SciencesEmory University

Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related *** of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in *** we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA *** of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and *** pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.

关键词： cell-type specific populations fear-related disorders central amygdala dopamine receptor 2

Brain-wide activation involved in 15 mA transcranial alternating current stimulation in patients with first-episode major depressive disorder

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General Psychiatry 2024年第2期37卷 265-273页

作者： Jie Wang Wenfeng Zhao Huang Wang Haixia Leng Qing Xue Mao Peng Baoquan Min Xiukun Jin Liucen Tan Keming Gao Hongxing Wang Songjiang Hospital and Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective DisordersShanghai Jiao Tong University School of MedicineShanghaiChina Institute of Neuroscience and Brain Diseases Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangHubeiChina division of Neuropsychiatry and Psychosomatics Department of NeurologyXuanwu Hospital of Capital Medical UniversityBeijingChina Electroconvulsive Therapy University Hospitals Cleveland Medical CenterClevelandOhioUSA Department of Psychiatry Case Western Reserve University School of MedicineClevelandOhioUSA Institute of Sleep and Consciousness disorders Center of EpilepsyBeijing Institute for Brain DisordersCapital Medical UniversityBeijingChina Institute of Special Medical Sciences School of Forensic MedicineShanxi Medical UniversityTaiyuanShanxiChina

Background Although 15 mA transcranial alternating current stimulation(tACS)has a therapeutic effect on depression,the activations of brain structures in humans accounting for this tACS configuration remain largely *** To investigate which intracranial brain structures are engaged in the tACS at 77.5 Hz and 15 mA,delivered via the forehead and the mastoid electrodes in the human *** Actual human head models were built using the magnetic resonance imagings of eight outpatient volunteers with drug-naïve,first-episode major depressive disorder and then used to perform the electric field distributions with SimNIBS *** The electric field distributions of the sagittal,coronal and axial planes showed that the bilateral frontal lobes,bilateral temporal lobes,hippocampus,cingulate,hypothalamus,thalamus,amygdala,cerebellum and brainstem were visibly stimulated by the 15 mA tACS *** Brain-wide activation,including the cortex,subcortical structures,cerebellum and brainstem,is involved in the 15 mA tACS intervention for first-episode major depressive *** results indicate that the simultaneous involvement of multiple brain regions is a possible mechanism for its effectiveness in reducing depressive symptoms.

关键词： stimulation involvement activation

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

Clinical features and treatment outcomes of major depressive disorder with genital symptoms

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Chinese Medical Journal 2024年第5期137卷 622-624页

作者： Xiaohui Wu Yuncheng Zhu Ping Sun Shuo Wang Zhiguo Wu Jia Huang Lan Cao Yun Wang Yousong Su Zhijian Yao Zuowei Wang Fan Wang Yong Wang Daihui Peng Jun Chen Yiru Fang Department of Clinical Research Center&division of Mood disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Department of Mood disorders Shanghai Hongkou Mental Health CenterShanghai 200083China Department of Psychiatry Nanjing Medical University Affiliated Brain HospitalNanjingJiangsu 210029China Department of Psychiatry&Affective disorders Center Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China Shanghai Key Laboratory of Psychotic disorders Shanghai 200118China

To the Editor:Major depressive disorder(MDD)is a mood disorder characterized by complex patterns of emotional,cognitive,and behavioral symptomology and deficits in daily *** symptoms,including a reduction in libido and menstrual disturbances,have been considered to be a classic symptom of MDD for many *** evidence has reached a broad consensus that the incidence of genital symptoms is higher in patients with MDD than in the general population.A systematic review and meta-analysis found a bidirectional association between MDD and genital symptoms,with patients with MDD showing a 50–70%increased risk of developing genital symptoms,while individuals with genital symptoms had a 130–210%increased risk of developing MDD.^([1])As previously reported,50–70%of people with MDD experience sexual dysfunction.^([2])To date,few studies have focused on the comparison of clinical features between patients with MDD with and without genital symptoms,and the longitudinal prognosis.

关键词： symptoms Clinical features